%0 Journal Article %T Immunobiology and conflicting roles of the human CD161 receptor in T cells. %A Wyrożemski Ł %A Qiao SW %J Scand J Immunol %V 94 %N 3 %D Sep 2021 %M 35611672 %F 3.889 %R 10.1111/sji.13090 %X Human C-type lectin-like CD161 is a type-II transmembrane protein expressed on the surface of various lymphocytes across innate and adaptive immune systems. CD161+ T cells displayed enhanced ability to produce cytokines and were shown to be enriched in the gut. Independently of function, CD161 was used as marker of innate-like T cells and marker of IL-17-producing cells. The function of CD161 is still not fully understood. In T cells, CD161 was proposed to act as co-signalling receptor that influence T-cell receptor-dependent responses. However, conflicting studies were published demonstrating lack of agreement over the role of CD161 during T-cell activation. In this review, we outline phenotypical and functional consequences of CD161 expression in T cells. We provide critical discussion over the most pressing issues including in depth evaluation of the literature concerning CD161 putative co-signalling properties.